Usefulness of Peripheral Vascular Function to Predict Functional Health Status in Patients With Fontan Circulation Bryan H. Goldstein, MD*, Jessica R. Golbus, Angela M. Sandelin, Nicole Warnke, BS, Lindsay Gooding, BS, Karen K. King, CCRC, Janet E. Donohue, MPH, James G. Gurney, PhD, Caren S. Goldberg, MD, MS, Albert P. Rocchini, MD, and John R. Charpie, MD, PhD After the Fontan operation, patients are at a substantial risk of the development of impaired functional health status. Few early markers of suboptimal outcomes have been identified. We sought to assess the association between peripheral vascular function and functional health status in Fontan-palliated patients. Asymptomatic Fontan patients (n  51) and age- and gender-matched healthy controls (n  22) underwent endothelial pulse amplitude testing using a noninvasive fingertip peripheral arterial tonometry (PAT) device. Raw data were transformed into the PAT ratio, an established marker of vascular function. Cardiopulmonary exercise testing was performed using the Bruce protocol. In the Fontan cohort, 94% of patients were New York Heart Association functional class I and 88% had a B-type natriuretic peptide level of <50 pg/ml. The baseline pulse amplitude, a measure that reflects the arterial tone at rest, was greater in the Fontan patients than in the controls (median 2.74, interquartile range 1.96 to 4.13 vs median 1.86, interquartile range 1.14 to 2.79, p  0.03). The PAT ratio, a measure of reactive hyperemia, was lower in Fontan patients (median 0.17, interquartile range 0.04 to 0.44, vs median 0.50, interquartile range 0.27 to 0.74, p  0.002). The key parameters of exercise performance, including peak oxygen consumption (median 28.8 ml/kg/min, interquartile range 25.6 to 33.2 vs median 45.5 ml/kg/min, interquartile range 41.7 to 49.9, p <0.0001) and peak work (median 192 W, interquartile range 150 to 246 vs median 330, interquartile range 209 to 402 W, p <0.0001), were lower in Fontan patients than in the controls. The PAT ratio correlated with the peak oxygen consumption (r  0.28, p  0.02) and peak work (r  0.26, p  0.03). In conclusion, in an asymptomatic Fontan population, there is evidence of reduced basal peripheral arterial tone and vasodilator response, suggesting dysfunction of the endothelium-derived nitric oxide pathway. Vasodilator function appears to correlate with exercise performance. © 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;108:428 – 434) Endothelial pulse amplitude tonometry (Endo-PAT) is a novel technique for the noninvasive assessment of periph- eral vascular function that was recently approved for clini- cal use by the United States Food and Drug Administration. In adults, Endo-PAT has been demonstrated to identify those with coronary artery dysfunction and to correlate with brachial artery reactivity testing (flow-mediated dilation). 1,2 Studies using Endo-PAT in children have been more lim- ited, but this technique has shown excellent reproducibility in an adolescent population. 3 Endo-PAT has been demon- strated to show evidence of abnormal vascular function in children and adolescents with insulin-dependent diabetes mel- litus. 4 Moreover, Endo-PAT might offer several practical ad- vantages over traditional noninvasive endothelial function test- ing, which has been hampered by technical difficulties in the pediatric age group. 5 In the present study, we used noninva- sive Endo-PAT testing to determine whether peripheral vas- cular function might be an early marker of altered functional health status in patients with a single ventricle after Fontan palliation. Methods The University of Michigan Institutional Review Board approved the present prospective study. Fontan subjects aged 8 to 25 years were identified through a search of the institutional pediatric cardiothoracic surgical database and approached for study participation. To reduce the risk to participants and reduce the effect of confounding variables, we excluded Fontan subjects with pacemaker dependence, severe hypoxemia (oxygen saturation 80% at rest), atrial arrhythmia requiring treatment in the previous 6 months, active protein-losing enteropathy, previous life-threatening ventricular arrhythmia or cardiac arrest outside of the im- mediate perioperative period, severe ventricular dysfunction or atrioventricular insufficiency, medically uncontrolled heart failure, systemic or pulmonary artery hypertension requiring therapy, or moderate to severe asthma. Age- and gender-matched control subjects were recruited from the local Division of Cardiology, Department of Pediatrics, C. S. Mott Chil- dren’s Hospital, University of Michigan Health System, Ann Arbor, Mich- igan. Manuscript received January 18, 2011; manuscript revised and ac- cepted March 18, 2011. This research was funded in part by grants from the Griese-Hutchinson- Woodson Champions for Children’s Hearts Fund and Michigan Congenital Heart Outcomes Research and Discovery Program (M-CHORD), both at the University of Michigan, Ann Arbor, Michigan. *Corresponding author: Tel: (513) 636-7072; fax: (513) 636-2410. E-mail address: bryan.goldstein@cchmc.org (B.H. Goldstein). 0002-9149/11/$ – see front matter © 2011 Elsevier Inc. All rights reserved. www.ajconline.org doi:10.1016/j.amjcard.2011.03.064